Antibody-dependent CD56 T cell responses are functionally impaired in long-term HIV-1 infectionReport as inadecuate




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Retrovirology

, 13:76

First Online: 04 November 2016Received: 29 July 2016Accepted: 30 October 2016

Abstract

BackgroundAntibody-dependent cellular cytotoxicity ADCC, which mainly mediated by natural killer NK cells, may play a critical role in slowing human immunodeficiency virus type-1 HIV-1 disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression.

ResultsIn the present study, we showed evidences that, in addition to NK cells, CD56+ T cells could generate degranulation upon CD16 cross-linking. Ex vivo study showed that FcγRIII CD16-mediated CD56+ T cell responses were distinctly induced by IgG antibody-bound P815 cells. Comparatively, CD56− T cells and invariant NKT CD3+ 6B11+ failed to induce antibody-dependent activation. Antibody-dependent CD56+ T cell responses were mainly ascribed to CD4-CD8 double negative subset and were functionally impaired in long-term HIV-1-infected former plasma donors, regardless of hepatitis C virus HCV coinfection status. Also, CD56+ T cell-mediated HIV-1-specific antibody-dependent responses were declined in men who have sex with men with HIV-1 infection over 3 years. Finally, we showed that matrix metalloprotease MMP inhibitor GM6001 could partially restored antibody-dependent CD56+ T cell responses of chronic HIV-1-infected subjects.

ConclusionsOur results suggested that CD56+ T cells could mediate ADCC responses and the responses were impaired in chronic HIV-1 infection.

KeywordsCD56+ T ADCC CD16 cross-linking Chronic HIV infection iNKT MMP inhibitor AbbreviationsADCCantibody-dependent cellular cytotoxicity

NKnatural killer

HIV-1human immunodeficiency virus type-1

HCVhepatitis C virus

MMPmatrix metalloprotease

AIDSacquired immune deficiency syndrome

iNKTinvariant NKT

TCRT cell receptor

α-GCα-galactosylceramide

MHCmajor histocompatibility complex

PBMCperipheral blood mononuclear cell

IFNγinterferon-γ

FPDsformer plasma donors

MSMmen who have sex with men

DNdouble negative subset

HESNHIV-exposed seronegative

6B11+Vα24-Jα18+

NKRnature killer cell receptor

CAP-CTMCobas Ampliprep-CobasTaqman

HBsAghepatitis B surface antigen

PFAparaformaldehyde

DMSOdimethyl sulphoxide

PMAphorbol-12-myristate-13-acetate

Xueying Fan and Liyan Zhu contributed equally to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s12977-016-0313-6 contains supplementary material, which is available to authorized users.

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Author: Xueying Fan - Liyan Zhu - Hua Liang - Zhe Xie - Xiangbo Huang - Shuo Wang - Tao Shen

Source: https://link.springer.com/article/10.1186/s12977-016-0313-6



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